2. Academic Validation
  3. Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment

Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment

  • Bioorg Med Chem Lett. 2004 Nov 1;14(21):5317-22. doi: 10.1016/j.bmcl.2004.08.024.
Ayako Yamashita 1,  Emily B Norton,  Joshua A Kaplan,  Chuan Niu,  Frank Loganzo,  Richard Hernandez,  Carl F Beyer,  Tami Annable,  Sylvia Musto,  Carolyn Discafani,  Arie Zask,  Semiramis Ayral-Kaloustian
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences and Oncology Research, Wyeth Research, Pearl River, NY 10965, USA. ay2122@columbia.edu
PMID: 15454219 DOI: 10.1016/j.bmcl.2004.08.024
Abstract

Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2.

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